METHODS: Six adult purpose-bred cats MATERIALS AND METHODS: Cats were administered 2 mg sotalol/kg body weight as a single intravenous bolus and as a single oral dose in a randomized crossover study with a two-week washout period. The same cats then received 3 mg sotalol/kg orally every 12 h for two weeks. Blood samples were collected at predetermined time points for 48 h postdose for quantification of sotalol using ultra-high-pressure liquid chromatography with mass spectrometry. Non-compartmental analysis was used to obtain pharmacokinetic parameters. Data are presented as median (min-max).
RESULTS: Following intravenous administration, plasma clearance and volume of distribution were 9.22 mL/min/kg (5.69-10.89 mL/min/kg) and 2175.56 mL/kg (1961-2341.57 mL/kg), respectively. Bioavailability was 88.41% (62.75-130.29) following a single oral dose. Peak plasma concentration (Cmax) and time to Cmax were 0.94 μg/mL (0.45-1.17 μg/mL) and 1.5 h (0.5-4 h) after a single oral dose (2 mg/kg), and 2.29 μg/mL (1.91-2.48 μg/mL) and 1.0 h (0.5-1.5 h) with chronic oral dosing (3 mg/kg), respectively. Elimination half-life was 2.75 h (2.52-4.10 h) and 4.29 h (3.33-5.53 h) for single and chronic oral dosing, respectively. Accumulation index was 1.17 (1.09-1.29) after chronic dosing. Urinary sotalol recovery was 81-108% of the intravenous dose.
CONCLUSIONS: Oral sotalol administration resulted in plasma concentrations reportedly efficacious in other species, with good to excellent oral bioavailability. Urinary excretion appears to be a major route of elimination. Following repeated oral dosing, minimal drug accumulation was estimated. Additional studies in cats are recommended due to the possibility of nonlinear kinetics.
方法:六只成年目的饲养的猫材料和方法:在一项随机交叉研究中,以单次静脉推注和单次口服剂量给猫服用2mg索他洛尔/kg体重,为期2周。然后,相同的猫每12小时口服3mg索他洛尔/kg,持续2周。在给药后48小时的预定时间点收集血液样品,以使用超高压液相色谱和质谱法定量索他洛尔。非房室分析用于获得药代动力学参数。数据表示为中值(min-max)。
结果:静脉注射后,血浆清除率和分布体积分别为9.22mL/min/kg(5.69-10.89)和2175.56(1961-2341.57)mL/kg,分别。在单次口服剂量后,生物利用度为88.41%(62.75-130.29)。单次口服剂量(2mg/kg)后,血浆峰值浓度(Cmax)和达到Cmax的时间为0.94μg/mL(0.45-1.17)和1.5h(0.5-4),和2.29μg/mL(1.91-2.48)和1.0h(0.5-1.5)与长期口服给药(3mg/kg),分别。单次和长期口服给药的消除半衰期为2.75h(2.52-4.10)和4.29h(3.33-5.53),分别。长期给药后积累指数为1.17(1.09-1.29)。尿索他洛尔的回收率为静脉内剂量的81-108%。
结论:口服索他洛尔导致在其他物种中有效的血浆浓度,具有良好至优异的口服生物利用度。尿液排泄似乎是消除的主要途径。反复口服给药后,估计最小的药物积累。由于非线性动力学的可能性,建议在猫中进行其他研究。